Transcript All In The Family: Identification, Evaluation, and

ALL IN THE FAMILY:
IDENTIFICATION,
EVALUATION, AND
MANAGEMENT OF
HEREDITARY CANCER
Regina Nuccio, MS, CGC
Clinical Director, Dept. of Genetic Counseling
Baptist Cancer Center
November 15 th , 2014
Disclosures
• I have no conflicts of interest to disclose
• Several graphics originally created by Andrea
Forman, MS, CGC and used with permission
INTRODUCTION
Typical Scenario
• A 35 y.o. healthy Caucasian woman comes to your
office for a routine wellness visit
• She tells you that her mother recently got diagnosed
with breast cancer, and that her grandmother also
had breast cancer
• Your patient wants to get “that Angelina Jolie test”
as soon as possible to determine her risks for breast
cancer
What is Genetic Counseling?
• “…the process of helping people understand and
adapt to the medical, psychological and familial
implications of genetic contributions to disease.” –
NSGC
• Detailed examination of personal and family history
(3-generation pedigree)
• In-depth discussion of risks, benefits, and limitations
of various testing options
• Psychosocial concerns
Patient Identification
Physician
Patient Request
Patient Referral
EPIC
Fax/Email
GC Preparation
Review Records
Contact patient
Comprehensive GC Session
Patient Education
Specimen Collection
Test Coordination
Shipment
Insurance
Results Disclosure
Performed by GC
Phone or in-person
Follow-up
Summary letter with recommendations
GC sends to patient
Who to Refer
Red flags
•Young age of onset of cancer (under age 50)
•Multiple primary cancers
•Multiple generations affected with cancer
•Rare cancers (e.g., male breast cancer)
•Certain ethnic backgrounds
•Known mutation in the family
Why Refer?
•Comprehensive nature of genetic counseling
•Accurate testing will be ordered
•Single site vs. full sequencing
•Correct genetic syndrome
•Most up-to-date information
•Testing options
•Cancer risks
•Patient satisfaction
Back to the scenario…
• You refer your patient for genetic counseling
• The GC takes the following pedigree:
Testing options
• BRCA is NOT the most appropriate choice for this
patient
• Breast cancer is on different sides of the family
• Ages of onset are not typical of hereditary breast
cancer syndrome
• More concerning cancers
• Better testing strategy:
• Test patient’s father for hereditary colon cancer
syndromes
• Offer patient single site testing if mutation is
discovered
REVIEW OF
HEREDITARY
SYNDROMES
Hereditary Breast and
Ovarian Cancer Syndrome
• BRCA1 and BRCA2
• Lifetime risks for cancer
• 40-80% for breast cancer (women)
• 11%-40% for ovarian cancer
• 1%-10% for male breast cancer (BRCA2)
• 1%-7% for pancreatic cancer
• Mutation carriers offered increased screening
(mammogram + breast MRI) and surgical options
(prophylactic mastectomies/BSO )
Lynch Syndrome
• MLH1, MSH2, MSH6, PMS2, EPCAM
• Lifetime risks for cancer
• 52%-82% for colorectal cancer
• 25%-60% for endometrial cancer
• 6%-13% for gastric cancer
• 4%-12% for ovarian cancer
• Mutation carriers are offered increased screening
(colonoscopy, endometrial biopsies) and surgical
options (TAH/BSO)
Familial Adenomatous Polyposis
• APC
• Attenuated form
• Lifetime risks
• ~100% for colon cancer (if no colectomy)
• polyps of the gastric fundus and duodenum
• osteomas
• dental anomalies
• congenital hypertrophy of the retinal pigment epithelium
(CHRPE)
• soft tissue tumors
• desmoid tumors
• Mutation carriers are offered a total colectomy (depending on
polyp burden) and screening for other cancers
Other syndromes
• PTEN harmartoma tumor syndrome
• Peutz-Jehgers syndrome
• Hereditary diffuse gastric cancer syndrome
• Hereditary melanoma
• Von-Hippel Lindau syndrome
GENETIC TESTING
STRATEGIES
Challenges in Genetic Testing
• Overlap of phenotypes between syndromes
• Limited or unknown family history
• Family history doesn’t fit the “classic” picture
• Insurance coverage
• “Testing fatigue”
Testing options
• Single gene
• High-risk panels (e.g., breast cancer genes only)
• Comprehensive panels (broad spectrum of genes)
Gene Panels
Buy One, Get a Dozen
Examples
• BRCAplus (Ambry)
• BRCA1, BRCA2, p53, PTEN, CDH1
• My Risk (Myriad)
• 25 genes (spectrum of syndromes)
• GeneDX, Invitae, University of Washington…
Advantages of Gene Panels
• Overlap of syndromes/phenotypes
• One sample = many tests
• Cost-effective
• Expansion of medical understanding
Disadvantages of Gene Panels
• Higher rate of variants of unknown significance
• May not be covered by insurance
• Uncertain management if mutation is found
• Longer turn-around time
CASE EXAMPLE
Options Offered
• BRCA only
• Likely negative given previous testing in her mother
• BRCAplus
• 5 genes which confer high risk for breast cancer
• Management recommendations clear
• MyRisk
• 25 genes
PALB2
• “Partner and localizer of BRCA2”
• Crucial to molecular stabilization of BRCA complex
• Older studies: increased risk for breast and
pancreatic cancers
• NEJM 2014: 33%-58% lifetime risk for breast cancer
Considerations From This Case
• Benefits
• Mutation found = explanation for family history
• Single-site testing now available
• Limitations
• Management?
• Pancreatic cancer risk?
Take-Home Message
• Ask family history questions
• Use your genetic counselors
When in doubt, refer!
Referral Information
• Regina Nuccio, MS, CGC
• 901-226-4064
• [email protected]
• Lorrell White, MS, CGC
• 901-226-4038
• [email protected]
• EPIC department: BMGAD
THANK
YOU!
References
• Antoniou AC, Casadei S, Heikkinen T, et al. Breast-cancer risk in
families with mutations in PALB2. N Engl J Med. 2014;371(6):497506.
• Gene Reviews:
• BRCA1 and BRCA2 Hereditary Breast and Ovarian Cancer
• Lynch Syndrome
• APC-Associated Polyposis Conditions